Recent studies
indicate that the downstream mediators of cardiac Ang II/TGF-β networking may
include Smad proteins, TGFβ1 -activated kinase-1 (TAK1), and
induction of hypertrophic responsiveness to h-adrenergic stimulation in cardiac
myocytes [46]. One study investigating the intracellular signaling events that
are required for AngIIdependent upregulation of TGF-β1 revealed that the induction
of TGF-β1 mRNA by Ang II in adult ventricular cardiomyocytes is mediated by
NAD(P)H oxidase, and subsequent activation of protein kinase C (PKC), p38- MAP
kinase, and nuclear Activating-Protein-1 (AP-1) binding activity [43] (Fig. 5),
Moreover,in cultured cardiac fibroblasts, Ang II directly promotes TGF-β11/Smad
signaling by elevating Smad 2 levels and inducing the translocation of
phosphorylated Smad 2 into the nuclei, and these responses also depend on the
AT1 receptor [80], indicating that cross-talk between Ang II and TGF-β1at
the postreceptor level (Smad signaling) may be associated with fibrosis in
cardiac remodeling.

Progressive
contractile dysfunction of viable myocardium that surrounds a large infarct
leads to heart failure following acute myocardial infarction (AMI) [91].
Experimental evidence indicates Stem cell-based therapy is being considered as
an alternative treatment for cardiomyopathy[38]. And may improve the left
ventricular (LV) contractile performance.In one study ,by comparig the effect of transplantation of (MAPCs), (BMCs) or fibroblasts on post-infarct cardiac function,they found transplantation of
MAPCs significantly improved LV contractile function for at least 8 weeks
post-transplantation; Significantly more inflammatory cells were present in
MAPC- than BMC-treated hearts at 1 week, which was accompanied by increased
vascularity 8 weeks post-transplantation.Later, they concluded MAPCs indirectly contributed to these
effects, by secreting MCP-1,VEGF,PDGF-BB,and TGFbeta1, and others, resulting in
increased angiogenensis and cardioprotection[91, 90].